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Dabrafenib
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Hodoodo CAT#: H205479

CAS#: 1195765-45-7 (free base)

Description: Dabrafenib, also known as GSK2118436 , is an orally bioavailable inhibitor of B-raf (BRAF) protein with potential antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations. On May 29, 2013, FDA approved this drug.

Chemical Structure

Dabrafenib

CAS# 1195765-45-7 (free base)

Instruction

Theoretical Analysis

Hodoodo Cat#: H205479
Name: Dabrafenib
CAS#: 1195765-45-7 (free base)
Chemical Formula: C23H20F3N5O2S2
Exact Mass: 519.10
Molecular Weight: 519.560
Elemental Analysis: C, 53.17; H, 3.88; F, 10.97; N, 13.48; O, 6.16; S, 12.34

Price and Availability

Size	Price	Availability
25mg	USD 150	Ready to ship
100mg	USD 250	Ready to ship
500mg	USD 650	Ready to ship
1g	USD 950	Ready to ship
2g	USD 1550	Ready to ship
5g	USD 2950	Ready to ship
10g	USD 4650	Ready to ship
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. Hodoodo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: GSK2118436A ( Dabrafenib ); GSK 2118436A; GSK-2118436A; GSK2118436B ( Dabrafenib Mesylate ); GSK-2118436B; GSK 2118436B. Trade name: Tafinlar.

IUPAC/Chemical Name: N-(3-(5-(2-aminopyrimidin-4-yl)-2-(tert-butyl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide

InChi Key: BFSMGDJOXZAERB-UHFFFAOYSA-N

InChi Code: InChI=1S/C23H20F3N5O2S2/c1-23(2,3)21-30-18(19(34-21)16-10-11-28-22(27)29-16)12-6-4-9-15(17(12)26)31-35(32,33)20-13(24)7-5-8-14(20)25/h4-11,31H,1-3H3,(H2,27,28,29)

SMILES Code: O=S(C1=C(F)C=CC=C1F)(NC2=CC=CC(C3=C(C4=NC(N)=NC=C4)SC(C(C)(C)C)=N3)=C2F)=O

Appearance: White to off-white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Related CAS# CAS#1195765-45-7 (Dabrafenib) CAS#1195768-06-9 (Dabrafenib mesylate)

Instruction:

View handling instruction

Biological target:	Dabrafenib (GSK2118436, GSK2118436A) is a mutant BRAFV600 specific inhibitor with IC50 of 0.7 nM in cell-free assays, with 7- and 9-fold less potency against B-Raf(wt) and c-Raf, respectively.
In vitro activity:	Vascular permeability was assessed to test the effects of dabrafenib on the PolyP-induced disruptions of the vascular barrier as the endothelial barrier integrity is cleaved by PolyP. Previous studies reported the PolyP parameters (50 μM and 4 h) that optimize the disruption of endothelial integrity. The cells were activated with PolyP (50 μM) for 4 h and then various concentrations of dabrafenib for 6 h. The results showed the inhibitory effects of dabrafenib on the PolyP-mediated hyperpermeability, with the optimal dose occurring at concentrations above 10 μM (Fig. 1A). Furthermore, dabrafenib alone (30 μM) did not alter the barrier integrity of the HUVECs (Fig. 1A). Reference: Chem Biol Interact. 2016 Aug 25;256:266-73. https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(16)30298-8
In vivo activity:	Dabrafenib was intravenously injected into mice with PolyP-mediated hyperpermeability. The results showed that PolyP enhanced vascular permeability, and this was suppressed by dabrafenib (Fig. 1B). Because the average blood volume is 72 mL/kg and the average weight of the mice that were used in this study was 27 g, the amount of dabrafenib (5.2, 10.4, 20.8, or 31.1 μg/mouse) injected was equivalent to 5, 10, 20, or 30 μM in peripheral blood. Reference: Chem Biol Interact. 2016 Aug 25;256:266-73. https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(16)30298-8

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	100.0	192.47

Preparing Stock Solutions

The following data is based on the product molecular weight 519.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:
In vitro protocol:	1. Lee S, Ku SK, Bae JS. Anti-inflammatory effects of dabrafenib on polyphosphate-mediated vascular disruption. Chem Biol Interact. 2016 Aug 25;256:266-73. doi: 10.1016/j.cbi.2016.07.024. Epub 2016 Jul 25. PMID: 27458080. 2. Jung B, Kang H, Lee W, Noh HJ, Kim YS, Han MS, Baek MC, Kim J, Bae JS. Anti-septic effects of dabrafenib on HMGB1-mediated inflammatory responses. BMB Rep. 2016 Apr;49(4):214-9. doi: 10.5483/bmbrep.2016.49.4.220. PMID: 26592934; PMCID: PMC4915240.
In vivo protocol:	1. Lee S, Ku SK, Bae JS. Anti-inflammatory effects of dabrafenib on polyphosphate-mediated vascular disruption. Chem Biol Interact. 2016 Aug 25;256:266-73. doi: 10.1016/j.cbi.2016.07.024. Epub 2016 Jul 25. PMID: 27458080. 2. Posobiec LM, Vidal JD, Hughes-Earle A, Laffan SB, Hart T. Early Vaginal Opening in Juvenile Female Rats Given BRAF-Inhibitor Dabrafenib Is Not Associated with Early Physiologic Sexual Maturation. Birth Defects Res B Dev Reprod Toxicol. 2015 Dec;104(6):244-52. doi: 10.1002/bdrb.21165. Epub 2015 Dec 1. PMID: 26626128.

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1: Banzi M, De Blasio S, Lallas A, Longo C, Moscarella E, Alfano R, Argenziano G. Dabrafenib: a new opportunity for the treatment of BRAF V600-positive melanoma. Onco Targets Ther. 2016 May 6;9:2725-33. doi: 10.2147/OTT.S75104. eCollection 2016. Review. PubMed PMID: 27226731; PubMed Central PMCID: PMC4866744.

2: Spain L, Julve M, Larkin J. Combination dabrafenib and trametinib in the management of advanced melanoma with BRAFV600 mutations. Expert Opin Pharmacother. 2016;17(7):1031-8. doi: 10.1517/14656566.2016.1168805. Epub 2016 Apr 12. Review. PubMed PMID: 27027150.

3: Zia Y, Chen L, Daud A. Future of combination therapy with dabrafenib and trametinib in metastatic melanoma. Expert Opin Pharmacother. 2015;16(14):2257-63. doi: 10.1517/14656566.2015.1085509. Epub 2015 Sep 2. Review. PubMed PMID: 26331795.

4: Giurcaneanu C, Nitipir C, Popa LG, Forsea AM, Popescu I, Bumbacea RS. Evolution of melanocytic nevi under vemurafenib, followed by combination therapy with dabrafenib and trametinib for metastatic melanoma. Acta Dermatovenerol Croat. 2015;23(2):114-21. Review. PubMed PMID: 26228819.

5: Khoja L, Hogg D. Dabrafenib in the treatment of metastatic or unresectable melanoma. Expert Rev Anticancer Ther. 2015 Mar;15(3):265-76. doi: 10.1586/14737140.2015.1014343. Review. PubMed PMID: 25711514.

6: Awad MM, Sullivan RJ. Dabrafenib in combination with trametinib for the treatment of metastatic melanoma. Expert Rev Clin Pharmacol. 2015 Jan;8(1):25-33. doi: 10.1586/17512433.2015.974556. Epub 2014 Dec 4. Review. PubMed PMID: 25473943.

7: McGettigan S. Dabrafenib: A New Therapy for Use in BRAF-Mutated Metastatic Melanoma. J Adv Pract Oncol. 2014 May;5(3):211-5. Review. PubMed PMID: 25089220; PubMed Central PMCID: PMC4114496.

8: Luke JJ, Ott PA. New developments in the treatment of metastatic melanoma - role of dabrafenib-trametinib combination therapy. Drug Healthc Patient Saf. 2014 Jun 24;6:77-88. doi: 10.2147/DHPS.S39568. eCollection 2014. Review. PubMed PMID: 25018652; PubMed Central PMCID: PMC4075957.

9: Rutkowski P, Blank C. Dabrafenib for the treatment of BRAF V600-positive melanoma: a safety evaluation. Expert Opin Drug Saf. 2014 Sep;13(9):1249-58. doi: 10.1517/14740338.2014.939954. Epub 2014 Jul 11. Review. PubMed PMID: 25014231.

10: Kainthla R, Kim KB, Falchook GS. Dabrafenib. Recent Results Cancer Res. 2014;201:227-40. doi: 10.1007/978-3-642-54490-3_14. Review. PubMed PMID: 24756796.

11: Kainthla R, Kim KB, Falchook GS. Dabrafenib for treatment of BRAF-mutant melanoma. Pharmgenomics Pers Med. 2013 Dec 31;7:21-9. doi: 10.2147/PGPM.S37220. eCollection 2014. Review. PubMed PMID: 24516336; PubMed Central PMCID: PMC3917541.

12: Trinh VA, Davis JE, Anderson JE, Kim KB. Dabrafenib therapy for advanced melanoma. Ann Pharmacother. 2014 Apr;48(4):519-29. doi: 10.1177/1060028013513009. Epub 2013 Nov 20. Review. PubMed PMID: 24259661.

13: Medina T, Amaria MN, Jimeno A. Dabrafenib in the treatment of advanced melanoma. Drugs Today (Barc). 2013 Jun;49(6):377-85. doi: 10.1358/dot.2013.49.6.1968669. Review. PubMed PMID: 23807941.

14: Luke JJ, Hodi FS. Ipilimumab, vemurafenib, dabrafenib, and trametinib: synergistic competitors in the clinical management of BRAF mutant malignant melanoma. Oncologist. 2013 Jun;18(6):717-25. doi: 10.1634/theoncologist.2012-0391. Epub 2013 May 24. Review. PubMed PMID: 23709751; PubMed Central PMCID: PMC4063399.

15: Gibney GT, Zager JS. Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies. Expert Opin Drug Metab Toxicol. 2013 Jul;9(7):893-9. doi: 10.1517/17425255.2013.794220. Epub 2013 Apr 29. Review. PubMed PMID: 23621583.

16: Menzies AM, Long GV, Murali R. Dabrafenib and its potential for the treatment of metastatic melanoma. Drug Des Devel Ther. 2012;6:391-405. doi: 10.2147/DDDT.S38998. Epub 2012 Dec 11. Review. PubMed PMID: 23251089; PubMed Central PMCID: PMC3523565.

17: Heneberg P. [Dabrafenib: the new inhibitor of hyperactive B-RAF kinase]. Klin Onkol. 2012;25(5):333-9. Review. Czech. PubMed PMID: 23102194.